The mechanism of neurotransmitter release will be investigated in the rat diaphragm and other mammalian nerve-muscle preparations. Both Poisson and binomial models of release are being considered. Trains of end-plate potentials will be evoked at different frequencies of stimulation and different quantal contents. Amplitudes of intracellularly recorded end-plate potentials will be measured by a digital computer which will examine the relationships between actual, estimated and theoretical quantal contents in order to define the statistical process associated with the release mechanism. Latency of neurotransmitter release will be determined under hypothermic conditions to further define the nature of the release mechanism. Special attention will be given the effects of neuromuscular blocking agents and neuromuscular facilitating agents on transmitter latency. In addition, the pharmacology and physiology of cricopharyngeal muscles isolated from dogs and sheep will be determined. Some of the muscles will be obtained from dogs with cricopharyngeal achalasia and an attempt will be made to determine the pathophysiology of this disease.